Assembly for a drug delivery device and drug delivery device with such an assembly

ABSTRACT

The present disclosure pertains to an assembly for a drug delivery device having a housing part, a piston rod displaceable relative to the housing part, a first sleeve member and a second sleeve member. First and second sleeve members are coupled to the housing part. In an initial state of the assembly the first sleeve member is movable from an initial position to a second position relative to the second sleeve member which allows the piston rod to axially travel from an initial position to a predetermined second position such that the assembly is in a primed state. Moreover, in the primed state of the assembly, with the first sleeve member being in the second position relative to the second sleeve member, first and second sleeve members are permanently rotationally and axially locked to each other by a first engagement feature such that first and second sleeve members together form a sleeve.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a U.S. National Phase Application pursuant to35 U.S.C. § 371 of International Application No. PCT/EP2014/054529 filedMar. 10, 2014, which claims priority to European Patent Application No.13159052.3 filed Mar. 13, 2013. The entire disclosure contents of theseapplications are herewith incorporated by reference into the presentapplication.

TECHNICAL FIELD

The present disclosure is generally directed to an assembly for a drugdelivery device and a respective drug delivery device comprising such anassembly.

BACKGROUND

Drug delivery devices have become widespread in the field of medicaltreatment where regular injection of a medicament by persons withoutformal medical training occurs. For example, this may be increasinglycommon among patients having diabetes where self-treatment enables suchpatients to conduct effective management of their disease.

There are different types of drug delivery devices. On the one hand, onecan differentiate between resettable devices which are reusable andnon-resettable devices which are disposable. For example, the disposabledelivery devices are supplied as self-contained devices. Suchself-contained devices do not have removable pre-filled cartridges.Rather, the pre-filled cartridges may not be removed and replaced fromthese devices without destroying the device itself.

On the other hand, one can differentiate between so-called fixed dosedevices which only allow dispensing of a predefined dose without thepossibility to increase or decrease the set dose and so-called variabledose devices which allow a user to individually select and dispense anumber of user variable doses of a medicament. In general, all thesetypes of delivery devices can be pen-shaped.

The drug delivery devices as explained above generally comprise severalprimary elements, for example a cartridge section that includes acartridge which can be contained within a housing or holder, a needleassembly connected to one end of the cartridge section, and anadditional assembly which may enable dialing and/or delivery of a doseof a medicament. The latter assembly can be connected to the end of thecartridge section which is located away from the needle assembly. Acartridge (often referred to as an ampoule) typically includes areservoir that is filled with a medication (for example insulin), amovable bung or piston or stopper located at one end of the cartridgereservoir, and a top having a pierceable seal or sheath located at theother, often necked-down end.

The assembly for dialing and/or delivering a dose of a medicament maycomprise a housing part and a piston rod or lead screw which isdisplaceable relative to the housing part. The piston rod is designed topush the bung or stopper of the cartridge in a direction to an outlet ofthe cartridge such that the medication can be expelled out of the deviceand delivered to a patient. In an initial state, for example a suppliedstate of the device, there can be a certain gap or clearance between theend of the piston rod and the bung of the cartridge when these parts areassembled. For example, the mentioned gap can be a consequence oftolerances associated with all or many of the assembled parts and/or thedesire not to pre-load the bung of the cartridge in the assembled stateof the device. The latter fact would have the consequence thatmedication might be unintentionally expelled out of the device.

A gap between the end of the piston rod and the cartridge bung can haveseveral disadvantages. One disadvantage may arise if a user takes thedevice for the first time for an intended injection of a predetermineddose of a medicament. The actual dose received will then be equal to thepredetermined dose less the initial air gap between the piston rod andthe bung. For example, this air gap is typically equivalent to a loss ofbetween 0 and 0.14 ml on the first dose. For many drugs, thisdiscrepancy can be significant and is well outside the allowable doseaccuracy limits. At present, it is conventional use, therefore, for theuser to be instructed to perform a so-called “air shot” which means thatthe user has to operate the device for the first time without injectingthe medication into his body but in the air until the gap between thepiston rod and the bung is traversed and fluid may begin to be ejected.

This course of action has the additional disadvantage that expensivemedication potentially has to be discarded before the user may take thefirst injection of the medicament. This may result in rising costs forthe medication and/or the drug delivery device.

It is, therefore, an object to describe an assembly for a drug deliverydevice as well as a drug delivery device with such an assembly which aredesigned so that the gap between the piston rod and the cartridge bungcan be removed (transition from an initial state to a primed state)before a first dose of a medicament is injected.

SUMMARY

In a first aspect, this object is solved by an assembly for a drugdelivery device according to claim 1. The assembly comprises a housingpart, a piston rod displaceable relative to the housing part, a firstsleeve member and a second sleeve member, first and second sleevemembers being coupled to the housing part. In an initial state of theassembly, the first sleeve member is movable from an initial position toa second position relative to the second sleeve member which allows thepiston rod to axially travel from an initial position to a predeterminedsecond position such that the assembly is in a primed state. In theprimed state of the assembly, with the first sleeve member being in thesecond position relative to the second sleeve member, first and secondsleeve members are permanently rotationally and axially locked to eachother by a first engagement feature such that first and second sleevemembers together form a sleeve.

The assembly provides features for a transition from an initial state,which may be a delivered state or delivered condition of the assembly,to a primed state in which the assembly is ready for a first dose of amedicament within a drug delivery device to be ejected out of thedevice. During the transition from the initial state to the primedstate, the piston rod is enabled to axially travel with respect to thehousing part of the assembly from an initial position to a predeterminedsecond position. That means, in the initial state of the assembly thepiston rod is enabled to axially travel with respect to the housing suchthat a gap or clearance between the piston rod and a cartridge bung of adrug delivery device, with the assembly assembled into the drug deliverydevice, can be removed or traversed. The axial travel or movement of thepiston rod from its initial position to its predetermined secondposition (i.e. the transition from the initial state to the primed stateof the assembly) is enabled by the first sleeve member being movablefrom a respective initial position to a respective second positionrelative to the second sleeve member of the assembly. That means, themovement of the first sleeve member relative to the second sleeve memberin the initial state of the assembly is related to the axial travel ofthe piston rod from its initial position to its predetermined secondposition.

In the primed state of the assembly, the first and second sleeve membersare permanently rotationally and axially locked to each other by a firstengagement feature, wherein first and second sleeve members togetherform a single sleeve. In the primed state, the first sleeve member isbrought in its second position relative to the second sleeve member.That means, upon movement of the first sleeve member from its initialposition to its second position relative to the second sleeve member,the further interaction of first and second sleeve members with otherparts of the assembly takes place in such a way that first and secondsleeve members can only be moved together and, therefore, have afunctional behavior of one single piece with regard to other parts ofthe assembly.

Since in the primed state of the assembly a movement of the first sleevemember relative to the second sleeve member is prevented (due to theirpermanently rotationally and axially locking interaction), a furthermovement of the piston rod as during the transition from the initialstate to the primed state of the assembly is prevented, too. That means,a transition of the piston rod from the initial state to the primedstate, i.e. an axial travel of the piston rod in order to perform thistransition, is only enabled as long as the first sleeve member ismovable relative to the second sleeve member. Once the first sleevemember has taken its second position relative to the second sleevemember, the assembly is in its primed state, wherein a further axialtravel of the piston rod in order to perform the transition into theprimed state is no longer possible.

The term “primed state” in this context shall be understood as a stateof the assembly in which the assembly is in a ready-to-use-state; thatmeans the assembly can be further operated by a user for dialing and/ordelivering a predetermined amount of a medicament when assembled into adrug delivery device. As such, the primed state provides a state inwhich “normal” operation of the assembly can be performed.

An initial movement of the first sleeve member relative to the secondsleeve member can be designed such that an axial travel of the pistonrod is delimited to a predetermined distance corresponding to an air gapbetween the end of the piston rod and a cartridge bung of a drugdelivery device in which the assembly can be used. The measures asexplained above have the advantage that the air gap can be traversedwithout the user being expected to perform “air shots” discardingmedication for preparing a drug delivery device for the first injection.The explained assembly provides features allowing a user to perform apriming action in order to transfer the assembly from its initial stateinto its primed state, i.e. to remove an air gap between the end of thepiston rod and the cartridge bung, in a convenient and simple way suchthat a drug delivery device in which the assembly is used can beprepared for the first use in a better way than is the case inconventional known solutions.

According to a first embodiment of the assembly, the functionalrelationship between the first and/or the second sleeve member and thepiston rod can be designed such that a movement of the first sleevemember relative to the second sleeve member only enables an axialmovement of the piston rod. That means, the axial travel of the pistonrod is not generated by a movement of the first sleeve member relativeto the second sleeve member, but is delimited and therefore in a sensecontrolled by the movement of the first sleeve member relative to thesecond sleeve member. An axial travel of the piston rod in this case isonly allowed as long as the first sleeve member is in fact movablerelative to the second sleeve member. When the first sleeve member is ina second position relative to the second sleeve member, no further axialtravel of the piston rod for priming the assembly is possible.

In this embodiment, an axial movement of the piston rod can, forexample, be generated by a user pushing the piston rod directly orindirectly via another coupling member in axial direction relative tothe housing part of the assembly.

According to an alternative second embodiment, the movement of the firstsleeve member relative to the second sleeve member not only controls ordelimits an axial travel of the piston rod, but also generates such amovement of the piston rod. In this case, first and second sleevemembers may act as direct or indirect driving members for driving thepiston rod. In this context, it is conceivable that a user operates thefirst sleeve member and moves it relative to the second sleeve membersuch that the piston rod (directly or indirectly coupled to the firstand/or second sleeve member) can axially travel from its initialposition to its second position, i.e. into the primed state of theassembly.

An important fact of all of the mentioned embodiments is that an axialmovement of the piston rod for traversing the assembly from its initialstate into its primed state can only be performed with the first sleevemember being movable relative to the second sleeve member. In the primedstate of the assembly, the first sleeve member is in its second positionrelative to the second sleeve member and is rotationally and axiallylocked to the second sleeve member and, therefore, cannot further moverelative to the second sleeve member. In this state, the assembly isfully primed, such that no further axial travel of the piston rod inorder to perform the transition into the primed state is necessary orallowed.

Certainly, the explained features do not prevent any further movement ofthe piston rod during the further use of the assembly. That would beagainst the intention of the assembly for dialing and/or delivering adose of a medicament as used in a drug delivery device. It is essentialthat any further operation of the assembly and any movement of thepiston rod relating therefrom are caused by means of features of theassembly, with first and second sleeve members together acting as onepiece or sleeve, respectively. The functionality of first and secondsleeve members as to enable the piston rod to axially move into a primedstate as explained above is completed during further operation of theassembly.

In one embodiment, the assembly may comprise a driver coupled to thepiston rod for driving the piston rod. That means any movement of thepiston rod (or only a selected movement of the piston rod) can be drivenby the driver. Hence, the driver may act as a coupling member between auser's operational action and a movement of the piston rod resultingtherefrom. In this aspect, the driver transmits an operational actioninto a movement of the piston rod.

Alternatively or in combination with this embodiment, the assembly maycomprise a button which may be arranged at a proximal end of theassembly and which may be coupled to the first sleeve member. In thecase that the assembly provides a driver as explained above, the buttonmay also be coupled to the driver. The button may provide anothercoupling feature, besides a potential driver, for coupling a user'soperational action with the movement of either or both of the firstsleeve member and the piston rod.

The term “proximal end” in this context means an end of the assemblywhich is in greater distance from a needle part of a drug deliverydevice in which the assembly is used than the other end of the assembly.This can mean for a drug delivery device, especially a pen-shapeddevice, with such an assembly that one end of the drug delivery deviceforms a needle assembly of a cartridge holder and the other end of thedrug delivery device is formed by the proximal end of the assembly asexplained above. Briefly, the proximal end of the assembly is the endthe most distant from a body site of a patient when operating a drugdelivery device for injection of a medicament into the body.

In the initial state of the assembly, the button is preferably enabledto axially travel relative to the second sleeve member, the buttonduring its axial travel entraining the driver such that the driver isaxially displaced relative to the housing part, thereby urging thepiston rod into its axial movement from the initial position to thepredetermined second position in order to bring the assembly into itsprimed state. In this embodiment, the button may be coupled to the firstsleeve member and to the driver, wherein the driver per se is coupled tothe piston rod. Accordingly, an axial movement of the button relative tothe second sleeve member is enabled by the first sleeve member beingmovable relative to the second sleeve member correspondingly.

The first sleeve member can, for example, be axially movable and/orrotatable with respect to the second sleeve member. During its axialtravel, the button entrains the driver such that the driver is axiallydisplaced relative to the housing part. The driver in turn urges thepiston rod into its axial movement from the initial position to theprimed position. This movement of the discrete parts button, driver, andpiston rod is enabled until the first sleeve member is in its secondposition relative to the second sleeve member. Once the first sleevemember has taken the latter position, a further axial travel of thebutton causing a transition of the piston rod from its initial positionto its primed position is no longer possible. In this embodiment, a usermay, for example, be instructed to press the button which is arranged atthe proximal end of the assembly for priming the assembly in order toprepare a drug delivery device in which the assembly is used for thefirst injection.

According to one embodiment, the first sleeve member engages with thesecond sleeve member via a second engagement feature such that in theinitial position of the first sleeve member, a maximum clearance betweenrespective walls of first and second sleeve members is limited to apredetermined clearance. That means a movement of the first sleevemember relative to the second sleeve member can be delimited via thesecond engagement feature. Hence, movement of the first sleeve memberrelative to the second sleeve member is controlled and delimited by apredetermined path and/or distance between respective walls and/or partsof first and second sleeve members. For example, a movement of the firstsleeve member is only admissible in order to traverse an initialclearance between first and second sleeve members, wherein the firstsleeve member can be moved towards the second sleeve member, but not ina direction away from the second sleeve member. This feature may havethe advantage that according to an embodiment, wherein a user mayoperate a button for priming the assembly can only press the button intoa housing of the assembly but cannot pull the button out of the housingof the assembly. Hence, this feature provides an easy-to-use functionenabling an improved handling of the assembly, especially for users withlimited dexterity.

According to one preferable embodiment, the movement of the first sleevemember from its initial position to its second position relative to thesecond sleeve member is non-reversible. Once the first sleeve member hasmoved from its initial position to its second position relative to asecond sleeve member and has consequently taken the second position, areverse movement of the first sleeve member back from the secondposition in a direction towards the first position is prevented. Thisfeature can be supported by the first engagement feature as explainedabove by which first and second sleeve members are permanentlyrotationally and axially locked to each other in the second position ofthe first sleeve member relative to the second sleeve member. Thenon-reversible feature as explained in this context has the advantagethat, once the assembly has been traversed from its initial state to itsprimed state, the assembly remains in the primed state during furtheroperation of the assembly. A subsequent manipulation of the first sleevemember for moving the first sleeve member relative to the second sleevemember is prevented in the primed state. Accordingly, the assembly takesa secure state after the transition from the initial state to the primedstate has been performed. Another advantage of the non-reversiblefeature is that a user may be enabled to easily spot whether theassembly is still in its initial state or already in its primed state.

According to one embodiment, the first sleeve member engages with thehousing part via a third engagement feature such that between theinitial position and the second position of the first sleeve memberrelative to the second sleeve member, a rotational movement of the firstsleeve member relative to the housing part is prevented. This featuredelimits a movement of the first sleeve member to an axial movement withrespect to the housing part during a transition from the initial stateto a primed state of the assembly. In an exemplary embodiment, the firstsleeve member in combination with either or both of a driver or a buttoncan only be axially moved with respect to the housing part, wherein thedriver and/or button are axially moved with respect to the housing part,too.

Hence, the assembly can be designed such that a user presses the buttonin an axial direction, wherein the first sleeve member (potentially incombination with the driver) is also axially moved with respect to thehousing. Accordingly, the piston rod travels axially into the primedstate as explained above. During this movement, a rotational movement ofeither or both of the button and the first sleeve member is prevented bythe above-explained feature. This has the advantage that, for example,any rotational dialing action (if such an action is permitted by thedesign and use of the assembly in combination with a respective drugdelivery device) is prevented as long as a transition of the assemblyfrom the initial state to the primed state has not been fully performed,and is firstly enabled, when the assembly has taken its primed statewith the piston rod having traversed the air gap between its end and acartridge bung of an assembled drug delivery device as explained in thecontext above. Therefore, such an assembly provides secure and improvedhandling, especially for a user with limited dexterity, since anyoperational movement is controlled by the assembly itself. A user cannotperform any wrong operational movement.

According to one embodiment, the second sleeve member comprises an innerthread engaging an outer thread of the housing part such that the secondsleeve member is movable on a helical path relative to the housing part.Additionally, first and second sleeve members can be in threadedengagement with each other, wherein the movement of the first sleevemember from its initial position to its second position relative to thesecond sleeve member urges the second sleeve member into a rotationalmovement relative to the housing part and to the first sleeve membersuch that the second sleeve member moves on the helical path relative tothe housing part in a direction opposite to the direction of movement ofthe first sleeve member.

The explained feature enables the second sleeve member to react on amovement of the first sleeve member relative to the second sleeve membersuch that the movement of the first sleeve member urges the secondsleeve member into a respective movement. This coupling is fulfilled bya threaded engagement of first and second sleeve members. For example,the first sleeve member can axially travel with respect to the housingpart of the assembly and with respect to the second sleeve member, suchthat due to the threaded engagement of the two members, the secondsleeve member is urged into a rotational movement relative to thehousing part and to the first sleeve member. Accordingly, the secondsleeve member rotates as long as the first sleeve member moves axiallywith respect to the housing part and the second sleeve member. By thisfeature, additional functionality of the assembly can be performed.

In this context, an additional functionality can, for example, be givenin such a way that during movement of the second sleeve member relativeto the housing part (caused by a movement of the first sleeve member asexplained above) a display information provided by the second sleevemember can be designed to change from an initial state information to aprimed state information. That means, movement of the second sleevemember can indicate the transition of the assembly from the initialstate to the primed state. As such, the movement of the first sleevemember relative to the second sleeve member can fulfill twofunctionalities. The first functionality is given by the explanationsabove, wherein a movement of the piston rod from its initial position toits predetermined second position, i.e. the primed state, is enabled aslong as the first sleeve member is movable relative to the second sleevemember. The second functionality is given in so far as first and secondsleeve members are coupled, wherein a movement of the first sleevemember causes a movement of the second sleeve member, for example inorder to indicate that a priming action is or has been performed.

Preferably, the second sleeve member is designed as so-called numbersleeve and provides dosing indicia for setting a predetermined dose of amedicament. With the dosing indicia indicating the doses of amedicament, a user can dial a dose by visually controlling the amount ofmedicament set in the assembly via the dosing indicia of the secondsleeve member.

According to another aspect, the above-mentioned object is also solvedby a drug delivery device for selecting and dispensing a number of dosesof a medicament, comprising a housing, a cartridge containing themedicament and an assembly of the type explained above.

The terms “medicament”, “medication” and “drug” as well as mentionedequivalents, as used herein, preferably mean a pharmaceuticalformulation containing at least one pharmaceutically active compound,

wherein in one embodiment the pharmaceutically active compound has amolecular weight up to 1500 Da and/or is a peptide, a proteine, apolysaccharide, a vaccine, a DNA, a RNA, an enzyme, an antibody or afragment thereof, a hormone or an oligonucleotide, or a mixture of theabove-mentioned pharmaceutically active compound,

wherein in a further embodiment the pharmaceutically active compound isuseful for the treatment and/or prophylaxis of diabetes mellitus orcomplications associated with diabetes mellitus such as diabeticretinopathy, thromboembolism disorders such as deep vein or pulmonarythromboembolism, acute coronary syndrome (ACS), angina, myocardialinfarction, cancer, macular degeneration, inflammation, hay fever,atherosclerosis and/or rheumatoid arthritis,

wherein in a further embodiment the pharmaceutically active compoundcomprises at least one peptide for the treatment and/or prophylaxis ofdiabetes mellitus or complications associated with diabetes mellitussuch as diabetic retinopathy,

wherein in a further embodiment the pharmaceutically active compoundcomprises at least one human insulin or a human insulin analogue orderivative, glucagon-like peptide (GLP-1) or an analogue or derivativethereof, or exendin-3 or exendin-4 or an analogue or derivative ofexendin-3 or exendin-4.

Insulin analogues are for example Gly(A21), Arg(B31), Arg(B32) humaninsulin; Lys(B3), Glu(B29) human insulin; Lys(B28), Pro(B29) humaninsulin; Asp(B28) human insulin; human insulin, wherein proline inposition B28 is replaced by Asp, Lys, Leu, Val or Ala and wherein inposition B29 Lys may be replaced by Pro; Ala(B26) human insulin;Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) humaninsulin.

Insulin derivates are for example B29-N-myristoyl-des(B30) humaninsulin; B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl humaninsulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin;B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30human insulin; B29-N—(N-palmitoyl-Y-glutamyl)-des(B30) human insulin;B29-N—(N-lithocholyl-Y-glutamyl)-des(B30) human insulin;B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin andB29-N-(w-carboxyheptadecanoyl) human insulin.

Exendin-4 for example means Exendin-4(1-39), a peptide of the sequenceH-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2.

Exendin-4 derivatives are for example selected from the following listof compounds:

H-(Lys)4-des Pro36, des Pro37 Exendin-4(1-39)-NH2,

H-(Lys)5-des Pro36, des Pro37 Exendin-4(1-39)-NH2,

des Pro36 Exendin-4(1-39),

des Pro36 [Asp28] Exendin-4(1-39),

des Pro36 [IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39); or

des Pro36 [Asp28] Exendin-4(1-39),

des Pro36 [IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39),

wherein the group -Lys6-NH2 may be bound to the C-terminus of theExendin-4 derivative;

or an Exendin-4 derivative of the sequence

des Pro36 Exendin-4(1-39)-Lys6-NH2 (AVE0010),

H-(Lys)6-des Pro36 [Asp28] Exendin-4(1-39)-Lys6-NH2,

des Asp28 Pro36, Pro37, Pro38Exendin-4(1-39)-NH2,

H-(Lys)6-des Pro36, Pro38 [Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,

H-des Asp28 Pro36, Pro37, Pro38 [Trp(O2)25] Exendin-4(1-39)-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36 [Met(O)14, Asp28] Exendin-4(1-39)-Lys6-NH2,

des Met(O)14 Asp28 Pro36, Pro37, Pro38 Exendin-4(1-39)-NH2,

H-(Lys)6-desPro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-Asn-(Glu)5 des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-Lys6-des Pro36 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,

H-des Asp28 Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25]Exendin-4(1-39)-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(S1-39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2;

or a pharmaceutically acceptable salt or solvate of any one of theafore-mentioned Exendin-4 derivative.

Hormones are for example hypophysis hormones or hypothalamus hormones orregulatory active peptides and their antagonists as listed in RoteListe, ed. 2008, Chapter 50, such as Gonadotropine (Follitropin,Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin),Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin,Buserelin, Nafarelin, Goserelin.

A polysaccharide is for example a glucosaminoglycane, a hyaluronic acid,a heparin, a low molecular weight heparin or an ultra low molecularweight heparin or a derivative thereof, or a sulphated, e.g. apoly-sulphated form of the above-mentioned polysaccharides, and/or apharmaceutically acceptable salt thereof. An example of apharmaceutically acceptable salt of a poly-sulphated low molecularweight heparin is enoxaparin sodium.

Antibodies are globular plasma proteins (˜150 kDa) that are also knownas immunoglobulins which share a basic structure. As they have sugarchains added to amino acid residues, they are glycoproteins. The basicfunctional unit of each antibody is an immunoglobulin (Ig) monomer(containing only one Ig unit); secreted antibodies can also be dimericwith two Ig units as with IgA, tetrameric with four Ig units liketeleost fish IgM, or pentameric with five Ig units, like mammalian IgM.

The Ig monomer is a “Y”-shaped molecule that consists of fourpolypeptide chains; two identical heavy chains and two identical lightchains connected by disulfide bonds between cysteine residues. Eachheavy chain is about 440 amino acids long; each light chain is about 220amino acids long. Heavy and light chains each contain intrachaindisulfide bonds which stabilize their folding. Each chain is composed ofstructural domains called Ig domains. These domains contain about 70-110amino acids and are classified into different categories (for example,variable or V, and constant or C) according to their size and function.They have a characteristic immunoglobulin fold in which two β sheetscreate a “sandwich” shape, held together by interactions betweenconserved cysteines and other charged amino acids.

There are five types of mammalian Ig heavy chain denoted by α, δ, ε, γ,and μ. The type of heavy chain present defines the isotype of antibody;these chains are found in IgA, IgD, IgE, IgG, and IgM antibodies,respectively.

Distinct heavy chains differ in size and composition; α and γ containapproximately 450 amino acids and δ approximately 500 amino acids, whileμ and ε have approximately 550 amino acids. Each heavy chain has tworegions, the constant region (C_(H)) and the variable region (V_(H)). Inone species, the constant region is essentially identical in allantibodies of the same isotype, but differs in antibodies of differentisotypes. Heavy chains γ, α and δ have a constant region composed ofthree tandem Ig domains, and a hinge region for added flexibility; heavychains μ and ε have a constant region composed of four immunoglobulindomains. The variable region of the heavy chain differs in antibodiesproduced by different B cells, but is the same for all antibodiesproduced by a single B cell or B cell clone. The variable region of eachheavy chain is approximately 110 amino acids long and is composed of asingle Ig domain.

In mammals, there are two types of immunoglobulin light chain denoted byλ and κ. A light chain has two successive domains: one constant domain(CL) and one variable domain (VL). The approximate length of a lightchain is 211 to 217 amino acids. Each antibody contains two light chainsthat are always identical; only one type of light chain, κ or λ, ispresent per antibody in mammals.

Although the general structure of all antibodies is very similar, theunique property of a given antibody is determined by the variable (V)regions, as detailed above. More specifically, variable loops, threeeach the light (VL) and three on the heavy (VH) chain, are responsiblefor binding to the antigen, i.e. for its antigen specificity. Theseloops are referred to as the Complementarity Determining Regions (CDRs).Because CDRs from both VH and VL domains contribute to theantigen-binding site, it is the combination of the heavy and the lightchains, and not either alone, that determines the final antigenspecificity.

An “antibody fragment” contains at least one antigen binding fragment asdefined above, and exhibits essentially the same function andspecificity as the complete antibody of which the fragment is derivedfrom. Limited proteolytic digestion with papain cleaves the Ig prototypeinto three fragments. Two identical amino terminal fragments, eachcontaining one entire L chain and about half an H chain, are the antigenbinding fragments (Fab). The third fragment, similar in size butcontaining the carboxyl terminal half of both heavy chains with theirinterchain disulfide bond, is the crystalizable fragment (Fc). The Fccontains carbohydrates, complement-binding, and FcR-binding sites.Limited pepsin digestion yields a single F(ab′)2 fragment containingboth Fab pieces and the hinge region, including the H—H interchaindisulfide bond. F(ab′)2 is divalent for antigen binding. The disulfidebond of F(ab′)2 may be cleaved in order to obtain Fab′. Moreover, thevariable regions of the heavy and light chains can be fused together toform a single chain variable fragment (scFv).

Pharmaceutically acceptable salts are for example acid addition saltsand basic salts. Acid addition salts are e.g. HCl or HBr salts. Basicsalts are e.g. salts having a cation selected from alkali or alkaline,e.g. Na+, or K+, or Ca2+, or an ammonium ion N+(R1)(R2)(R3)(R4), whereinR1 to R4 independently of each other mean: hydrogen, an optionallysubstituted C1-C6-alkyl group, an optionally substituted C2-C6-alkenylgroup, an optionally substituted C6-C10-aryl group, or an optionallysubstituted C6-C10-heteroaryl group. Further examples ofpharmaceutically acceptable salts are described in “Remington'sPharmaceutical Sciences” 17. ed. Alfonso R. Gennaro (Ed.), MarkPublishing Company, Easton, Pa., U.S.A., 1985 and in Encyclopedia ofPharmaceutical Technology.

Pharmaceutically acceptable solvates are for example hydrates.

Preferable and/or alternative embodiments as well as further features ofan assembly and of a drug delivery device of the type explained aboveare disclosed and described in the depending claims as well as withreference to the accompanying drawings, in which:

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 shows a side view of a drug delivery device in an initial statein accordance with the present disclosure;

FIG. 2 shows the drug delivery device according to FIG. 1 in a primedstate;

FIG. 3 shows a side view of parts of the drug delivery device accordingto FIG. 1;

FIG. 4 shows a side view of parts of the drug delivery device accordingto FIG. 2;

FIG. 5 shows a translucent side view of inner parts of the drug deliverydevice according to FIG. 1;

FIG. 6 shows a translucent side view of inner parts of the drug deliverydevice according to FIG. 2;

FIG. 7 shows a perspective view of parts of a drug delivery deviceaccording to FIGS. 1 and 2 in a third state; and

FIG. 8 shows a perspective cut view of parts of a drug delivery deviceaccording to FIGS. 1 and 2.

DETAILED DESCRIPTION

FIG. 1 shows a side view of a drug delivery device 1 in an initial stateof the drug delivery device 1. The drug delivery device 1 comprises acartridge 2 and an outer housing 3 which is coupled to the cartridge 2and accommodates components of an assembly for dialing and/or dispensingmedication out of the cartridge 2 for delivery to a patient.

The cartridge 2 may contain a predetermined amount of a medication andprovides a thread feature at its left end for mounting a needle assembly(not shown) in order to inject the medication out of the cartridge 2into a body site of a patient. Moreover, the cartridge 2 provides a bungor stopper (not shown) which is arranged inside the cartridge 2 andwhich can be pushed towards the left end of the drug delivery device 1,i.e. towards the thread feature for the needle assembly of the cartridge2, in order to expel the medication out of the cartridge 2 via apredetermined pressure force.

The outer housing 3 accommodates, besides other parts and componentswhich are explained below, a piston rod (not shown) which is designed tobe driven by a user's operational action in order to push a bung of thecartridge 2 in the left direction for expelling the medicament out ofthe device 1. In particular, the piston rod can be driven by componentsand members as explained below.

Besides a piston rod, the outer housing 3 accommodates other parts andcomponents of which display information 5 (through a translucent windowin the outer housing 3) and a button 4 as well as a part of an innercomponent of the outer housing 3 are shown. The button 4 is arranged ata right end of the drug delivery device 1.

In general, the left end of the device 1 is called “distal end” and islocated the nearest to a body site of a patient during intendedoperation of the drug delivery device 1 for injection of the medicamentinto the body of the patient. The right end of the device 1 is called“proximal end” and is located the most distant from a body site of apatient.

In the initial state of the device 1 according to FIG. 1, a delivered orsupplied state of the device 1 is depicted. That means, the device 1 asshown in FIG. 1 is supplied to a user. In this state, there is an airgap (not shown in FIG. 1, explained in the context of FIG. 8) betweenthe cartridge bung and one end of the piston rod which during intendedoperation abuts the bung of the cartridge for medication delivery asexplained above. The air gap can be a consequence of tolerancesassociated with all assembled parts of the device 1 and results from thedesire not to pre-load the cartridge bung axially in left direction inthe assembled device in order to prevent unintended injection ofmedication out of the device 1.

The air gap between the piston rod and the bung can be traversed by atransition of the drug delivery device 1 from the initial state asdepicted in FIG. 1 to a so-called “primed state” according to FIG. 2,wherein in the primed state the piston rod has been axially moved suchthat it abuts with one end at the bung of the cartridge 2, a furtheraxial travel of the piston rod effecting an ejection of medicament outof the device 1.

FIG. 2 shows the device 1 according to FIG. 1, but now in the primedstate, with the button 4 being pressed in left direction into the outerhousing 3 (see the arrow). Consequently, the display information 5 hasbeen changed from a priming indicia according to FIG. 1 into aready-to-operate indicia (e.g. the number “0” to indicate readiness ofthe device 1) according to FIG. 2.

According to the embodiment of FIGS. 1 and 2, the axial travel of thebutton 4 from the initial position according to FIG. 1 into the primedposition according to FIG. 2 causes the piston rod within the outerhousing 3 of the device 1 to axially travel in left direction, whereinits axial travel is designed such that in the primed position accordingto FIG. 2, the piston rod abuts the cartridge bung of the cartridge 2,with the device 1 being ready for further operation. Further operationof the device 1 is explained in the context of FIGS. 7 and 8.

FIGS. 3 and 4 show interior parts and components of the drug deliverydevice 1 according to FIGS. 1 and 2 which are at least partlyaccommodated by the outer housing 3 of the device 1. FIG. 3 shows a partof the device in the initial state according to FIG. 1, wherein FIG. 4shows a part of the device in the primed state according to FIG. 2. Inboth FIGS. 3 and 4, the outer housing 3 is hidden in order to betterillustrate the mechanical interaction of the several components withinthe device 1.

FIG. 3 depicts a part of an inner housing 10, a first sleeve member 6, asecond sleeve member 7 and a button 4 (see also FIGS. 1 and 2). Firstand second sleeve members 6, 7 are arranged around an outer part of theinner housing 10. The button 4 is coupled to the first sleeve member 6,wherein the first sleeve member 6 is movable with respect to the secondsleeve member 7. That means, the first sleeve member 6 can be moved fromits initial position with respect to the second sleeve member 7according to FIG. 3 into a second position with respect to the secondsleeve member 7 according to FIG. 4. In particular, by pressing thebutton 4 in left direction, the first sleeve member 6 can axially traveltogether with the button 4 in left direction such that a transition ofthe components from the situation as depicted in FIG. 3 to the situationas depicted in FIG. 4 can be performed.

In detail, an axial travel of the button 4 together with the firstsleeve member 6 in left direction urges the second sleeve member 7 intoa rotational movement with respect to the inner housing 10 and the firstsleeve member 6, since first and second sleeve members 6, 7 are inthreaded engagement with each other. According to FIGS. 3 and 4,respective walls of a thread section (i.e. a section with an axial and acircular portion) interact with each other such that an axial movementof the first sleeve member 6 in left direction urges the second sleevemember 7 into a rotational movement.

The first sleeve member 6 provides an engagement feature 8 whichinteracts with the second sleeve member 7 in order to delimit themaximum axial clearance between first and second sleeve members 6, 7 toan axial clearance as depicted in FIG. 3 (the initial position of thecomponents). That means, the first sleeve member 6 cannot be moved inthe right direction away from the second sleeve member 7. This providesa safety feature for preventing that a user pulls the first sleevemember 6 with the button 4 out of the drug delivery device 1 in rightdirection. Only a movement in left direction of the button 4 togetherwith the first sleeve member 6 is permitted.

FIG. 4 shows the situation, when the button 4 and the first sleevemember 6 have traveled in left direction towards the second sleevemember 7, wherein the second sleeve member 7 has rotated caused by thethreaded engagement with the first sleeve member 6. In this way, thesecond sleeve member 7 has traveled on a helical path with respect tothe inner housing 10 due to a threaded engagement of an inner thread 11of the second sleeve member 7 with an outer thread 12 of the innerhousing 10. In this way, display information 5 showing a priming indicia(symbolized with a white P on a colored background) according to FIG. 3has been changed to a display information 5 (symbolized by the number“0”) indicating a ready-to-use state or primed state of the deviceaccording to FIG. 4. That means, the priming indicia has rotated inclockwise direction as symbolized by a circular arrow as depicted inFIG. 4.

In the state of FIG. 4, first and second sleeve members 6, 7 are inkeyed contact with each other, wherein the first sleeve member 6 nowengages with the second sleeve member 7 via another engagement feature9, besides the first engagement feature 8, such that first and secondsleeve members 6, 7 are permanently rotationally and axially locked toeach other. That means, first and second sleeve members 6, 7 togetherform a single piece or sleeve 14. Further operation of the componentscan only be fulfilled with first and second sleeve members 6, 7 togethermoving in a consistent way. With the aid of the second engagementfeature 9, a relational movement of first and second sleeve members 6, 7to each other as for a transition between FIGS. 3 and 4 isnon-reversible, which means that the first sleeve member 6 cannot beseparated anymore from the second sleeve member 7 when the first sleevemember 6 has reached its position according to FIG. 4.

The axial clearance between respective walls of first and second sleevemembers 6, 7 according to FIG. 3 enables the first sleeve member 6 tomove with respect to the second sleeve member 7 in the left direction.This in turn enables the button 4 to move together with the first sleevemember 6, as explained above, in left direction, such that thetransition between FIGS. 3 and 4 can be performed (see axial arrows inFIG. 4). The axial travel of the button 4 and the first sleeve member 6causes a piston rod (not shown in FIGS. 3 and 4) to axially move in leftdirection such that the piston rod can be traversed from an initialposition to a predetermined second position which provides the primedstate of a drug delivery device 1 as explained in the context of FIGS. 1and 2. When the button 4 and in particular the first sleeve member 6 arein the second position with respect to the second sleeve member 7 asdepicted in FIG. 4, a further axial travel of the piston rod during sucha movement of the button 4 and the first sleeve member 6 with respect tothe second sleeve member 7 is prevented. That means, the situation inFIG. 4 illustrates a secure state of the drug delivery device 1, whereinan air gap between an end of the piston rod and a cartridge bung of thecartridge 2 is removed.

FIGS. 5 and 6 represent a translucent view of inner parts of thecomponents according to FIGS. 3 and 4. FIG. 5 represents the initialstate according to FIGS. 1 and 3, wherein FIG. 6 represents a primedstate according to FIGS. 2 and 4.

According to FIG. 5, the first sleeve member 6 is in its outer positionwith respect to the second sleeve member 7, wherein the first sleevemember 6 provides a third engagement feature 15 preventing a rotationalmovement of the first sleeve member 6 with respect to the inner housing10. In this way, the engagement feature 15 lies in a cutout between twothreaded sections of an outer thread 13 of the inner housing 10 andblocks any rotational movement of the first sleeve member 6 with respectto the housing 10. Hence, the first sleeve member 6 can only be axiallymoved with respect to the inner housing 10 towards a predetermined stopposition 18 in order to traverse the assembly from the initial positionaccording to FIGS. 1 and 3 into the primed position according to FIGS. 2and 4.

FIG. 6 shows the first sleeve member 6 in its second position relativeto the second sleeve member 7 according to FIG. 4, wherein theengagement feature 15 now lies in a bay of the threaded section of theouter thread 13 of the inner housing 10. In this position the firstsleeve member 6 is enabled to rotate with respect to the inner housing10 such that the first sleeve member 6 can travel on a helical path inthe outer thread 13 with respect to the inner housing 10. In theposition according to FIG. 6, corresponding to the position of FIG. 4,first and second sleeve members 6, 7 can together travel on a helicalpath with respect to the inner housing 10, wherein the first sleevemember 6 travels in the outer thread 13 and the second sleeve member 7travels in the outer thread 12 of the inner housing 10. Moreover, thedefined stop feature 18 (cf. FIG. 5) provides a predetermined positionof the first sleeve member 6 relative to the inner housing 10 andelimits the further helical movement of the first sleeve member 6. Thestop position according to FIG. 6 can, for example, be an initialdialing position from which any dialing of a predetermined amount ofmedication can be started. Accordingly, the assembly may return to thisdiscrete position after a dose of a medicament has been delivered to apatient in order to enable subsequent dialing of another dose againstarting from this position.

The third engagement feature 15 according to FIGS. 5 and 6 has theadvantage that a rotational movement of the first sleeve member 6together with the button 4 is prevented as long as the assembly has notbeen securely traversed into the primed state. That means, a user has toperform an axial movement of the button 4 together with the first sleevemember 6 in order to prime the assembly or the drug delivery device 1,respectively, before, for example, a rotational dialing movement of thebutton 4 together with first and second sleeve members 6, 7 can beperformed. Hence, the third engagement feature 15 helps to improve thehandling of the device and prevents unintentional or unwilling operationof the device, especially for persons with limited dexterity.

FIG. 7 shows an operational state of components according to FIGS. 3 to6, after the assembly has been primed. In particular, FIG. 7 shows adialing state in which a predetermined amount of a medicament, i.e. apredetermined dose, has been dialed. For this purpose, the button 4 andthe first sleeve member 6 together with the second sleeve member 7 havebeen rotated, wherein first and second sleeve members 6, 7 have traveledon a helical path with respect to the inner housing 10 in rightdirection away from the inner housing 10, such that the button 4 and thefirst sleeve member 6 project in right direction out of the outerhousing 3. Towards the inner housing 10, the outer housing 3 has acutout and is hidden in order to improve better illustration of thethreaded engagement between first and second sleeve members 6, 7 andinner housing 10, without having any influence on the mechanicalbehavior of the assembly.

During the dialing action, display information 5 is given whichindicates a predetermined dose of a medicament. FIG. 7 shows anintermediate stage of dialing (for example 47 of 80 units).

The button 4 together with sleeve members 6, 7 can be moved from theposition as depicted in FIG. 7 axially in the left direction towards theinner housing 10 in order to urge a piston rod (not shown) into axialmovement with respect to the inner housing 10, such that the dialed doseof a medicament can be expelled out of a cartridge outlet correspondingto a device 1 according to FIGS. 1 and 2.

FIG. 8 shows a perspective cut view of the inner housing 10accommodating a piston rod 17, a driver 16 and at least partly a button4. The button 4 is coupled to the driver 16, such that a movement of thebutton 4 is transmitted to the driver 16. In detail, when the button 4is rotated, the driver 16 is also rotated (for dialing a dose accordingto FIG. 7, for example); when the button 4 is axially moved with respectto the inner housing 10, the driver 16 also does so.

Additionally, the driver 16 is threadedly coupled with the piston rod 17(see arrow), such that an axial movement of the driver 16 in the leftdownward direction urges the piston rod 17 into a helical movement suchthat the piston rod 17 also is driven into the left downward direction.The piston rod 17 can provide any thread feature for threaded engagementwith the driver 16. For example, the piston rod 16 can provided a twinthread arrangement.

In particular, FIG. 8 depicts a transition from an initial position ofthe piston rod 17 into a primed position of the piston rod 17, in whichposition the piston rod 17 abuts a bung 19 of a cartridge 2 according toFIGS. 1 and 2. In this way, an intentional gap between the piston rod 17in its initial position and a bung 19 of a cartridge 2 can be removed.This can be done by moving the button 4 together with the first sleevemember 6 according to the explanations in the context of FIGS. 3 and 4.

Upon transition of the piston rod 17 into its primed position (seeposition of piston rod 17 as depicted in FIG. 8), the assembly can beused to dial and dispense predetermined doses of a medicament, whereindialing takes place according to the explanations in the context of FIG.7, and wherein dispensing takes place according to the explanations inthe context of FIG. 8. The latter operation takes place by axiallypressing the button 4 and the driver 16 in the direction of the bung 19in the inner housing 10, such that the piston rod 17 is also driven inaxial direction and pushes the bung 19 such that medication can beexpelled out of a cartridge 2 of the device 1 according to FIGS. 1 and2.

The described embodiments are only exemplary embodiments withoutrestricting the basic idea of the disclosure, wherein a transition of anassembly for a drug delivery device from an initial state into a primedstate may be performed, with the first and second sleeve members 6, 7being movable to each other in the initial state and being permanentlyrotationally and axially locked to each other in a primed state. Thisenables a piston rod to be traversed from an initial position to apredetermined second position in which the piston rod is in a primedstate. In this way, an air gap between the piston rod and a cartridgebung in an initial state of the assembly can be removed. This helps forbetter handling and preparing a drug delivery device for furtheroperation, without the need of performing “air shots” and discardingexpensive medication for priming the drug delivery device.

The invention claimed is:
 1. Assembly for a drug delivery devicecomprising a housing part, a piston rod displaceable relative to thehousing part, a first sleeve member and a second sleeve member, firstand second sleeve members being coupled to the housing part, wherein inan initial state of the assembly the first sleeve member is movable froman initial position to a second position relative to the second sleevemember, wherein movement of the first sleeve member relative to thesecond sleeve member in the initial state of the assembly is related toan axial travel of the piston rod from an initial position to apredetermined second position which allows the piston rod to axiallytravel from its initial position to its predetermined second positionsuch that the assembly is in a primed state, wherein the first sleevemember engages with the housing part via a third engagement feature suchthat between the initial position and the second position of the firstsleeve member relative to the second sleeve member a rotational movementof the first sleeve member relative to the housing part is prevented,wherein in the primed state of the assembly, with the first sleevemember being in the second position relative to the second sleevemember, first and second sleeve members are permanently rotationally andaxially locked to each other by a first engagement feature such thatfirst and second sleeve members together form a sleeve, and wherein oncethe assembly has been traversed from its initial state to its primedstate, the assembly remains in the primed state during further operationof the assembly.
 2. The assembly according to claim 1, comprising adriver coupled to the piston rod for driving the piston rod.
 3. Theassembly according to claim 2, comprising a button arranged at aproximal end of the assembly and coupled to the first sleeve member andto the driver.
 4. The assembly according to claim 3, wherein in theinitial state of the assembly the button is enabled to axially travelrelative to the second sleeve member, the button during its axial travelentraining the driver such that the driver is axially displaced relativeto the housing part, thereby urging the piston rod into its axialmovement from the initial position to the predetermined second position.5. The assembly according to claim 3, wherein in the second position ofthe first sleeve member relative to the second sleeve member for dosesetting the button is rotatable which entrains the driver and first andsecond sleeve members such that the button, the driver and first andsecond sleeve members are moved on a helical path relative to thehousing part and the piston rod, and for dose dispensing the button isaxially displaceable which entrains the driver and first and secondsleeve members such that the button, the driver and first and secondsleeve members are axially moved relative to the housing part and thepiston rod, with first and second sleeve members and the piston rodrotating relative to the housing part, the button and the driver.
 6. Theassembly according to claim 1, wherein the first sleeve member engageswith the second sleeve member via a second engagement feature such thatin the initial position of the first sleeve member a maximum clearancebetween respective walls of first and second sleeve members is limitedto a predetermined clearance.
 7. The assembly according to claim 1,wherein the movement of the first sleeve member from its initialposition to its second position relative to the second sleeve member isnon-reversible.
 8. The assembly according to claim 1, wherein thehousing part comprises a first outer thread and wherein in the secondposition of the first sleeve member relative to the second sleeve memberthe third engagement feature engages with the first outer thread of thehousing part such that the first sleeve member is movable on a helicalpath relative to the housing part.
 9. The assembly according to claim 8,wherein the first outer thread of the housing part is designed such thatit delimits a predetermined stop position of the third engagementfeature relative to the housing part.
 10. The assembly according toclaim 1, wherein the second sleeve member comprises an inner threadengaging a second outer thread of the housing part such that the secondsleeve member is movable on a helical path relative to the housing part.11. The assembly according to claim 10, wherein first and second sleevemembers are in threaded engagement with each other, and wherein themovement of the first sleeve member from its initial position to itssecond position relative to the second sleeve member urges the secondsleeve member into a rotational movement relative to the housing partand to the first sleeve member such that the second sleeve member moveson the helical path relative to the housing part in a direction oppositeto the direction of movement of the first sleeve member.
 12. Theassembly according to claim 11, wherein during movement of the secondsleeve member on the helical path relative to the housing part a displayinformation provided by the second sleeve member is designed to changefrom an initial state information to a primed state information.
 13. Theassembly according to claim 1, wherein the second sleeve member providesdosing indicia for setting a predetermined dose of a medicament.
 14. Adrug delivery device for selecting and dispensing a number of doses of amedicament, comprising a housing, a cartridge containing the medicamentand an assembly according to claim 1.